Alzheimer's researchers see advances, setbacks

March 23, 2010 8:16:08 PM PDT
Recent developments in Alzheimer's research are underscoring the hope and frustration involved in trying to conquer the disease. While potential treatments are moving forward, others have taken a step back.

Former teacher Jean Simpson can still rip through a crossword puzzle with the vocabulary she has built over decades, but at the same time, she no longer has enough short-term memory to read a book.

"I can't remember once I get to page six. It's like, 'Whoops. What was that they said back there?'" she says.

She is taking part in a phase three clinical trial, testing a new drug that shows promise for treating Alzheimer's disease. It is an open-label trial which means all patients will receive the drug Bapineuzumab.

Alzheimer's researcher Jerome Goldstein says it is "a medication that addresses the plaques, the amaloy plaques in Alzheimer's disease."

Dr. Goldstein says a new imaging technique has allowed researchers to document the drug's effect on the brains of Alzheimer's patients, where it was recently shown to reduce clumps of plaque associated with the disease. In clinical trials, patients also showed some slowing of their memory loss.

"At the present time, we see some degree of stabilizations of the disorder," Goldstein says.

But, in a battle where even marginal progress is a victory, he is still cautious about any long-term predictions for Bapinuezumab.

In early March, another highly-publicized drug, developed in part by Bay Area start-up Medivation, failed a late-stage clinical trial. The future of that drug, Dimebon, is now unclear.

"The main point here is that we're 100 years into knowing the description of Alzheimer's disease without any effective treatment," says Dr. Dale Bredesen at the Buck Institute for Age Research in Marin County.

The Buck Institute is one of several labs now working on alternative targets for Alzheimer's drugs.

"We have a completely different view of this disease and it used to be thought that the plaques were the bad actors and it looks more now like they're the garbage dumps. Yes, they can smell bad. Yes, they can look bad, but they're not the most important thing," Bredesen says.

Buck Institute researchers have focused on a protein that helps guide nerves and their connections in the brain, rather than targeting the plaque. A video provided by the Buck Institute shows mice, genetically-altered with the same mutation found in people with Alzheimer's can no longer swim to their target in the pool. But, when scientists alter the protein, the mice quickly find their goal.

That research has evolved and scientists have found the addition of a protein called Netrin-1 has a similar effect.

At Goldstein's San Francisco clinic, Jean Simpson is hoping the current trial of Bapineuzumab will eventually lead to a new therapy to slow the symptoms of a disease that now affects more than five million people in the U.S.

"So, if they find something with one of us, we've gained, and that's why I'm here," Simpson says. "I just hope that it works and can help others."

Johnson & Johnson, the parent company of Elan -- the group that is testing Bapineuzumab -- has announced that they are extending the length of the clinical trial before they release results. Researchers say the company wants a larger pool of patients before they take their data to the FDA.


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